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Glucagon-Like Peptide Receptor Family

Glucagon-like peptide receptor is a family of G protein-coupled receptors. The glucagon-like peptide 1 receptor (GLP1R) is a receptor protein found on beta cells of the pancreas. Here show the two galanin receptors in humans including GLP1R and GLP2R, which are encoded by GLP1R (present on chromosome 6) and GLP2R (present on chromosome 17).

GLP1R is composed of two domains, one extracellular (ECD) that binds the C-terminal helix of GLP-1, and one transmembrane (TMD) domain that binds the N-terminal region of GLP-1. GLP1R binds glucagon-like peptide-1 (GLP1) and glucagon as its natural endogenous agonists. It is involved in the control of blood sugar level by enhancing insulin secretion. Consequently, GLP1R has been a target for developing drugs usually referred to as GLP1R agonists to treat diabetes. GLP1R is also expressed in the brain, stomach, and intestines. It is involved in the control of appetite, breathing, and heart rate. The diabetic, pancreatic, and neuroprotection implications of GLP1R are also thought to be potential therapies for treating diabetes and energy metabolism abnormalities associated with Huntington's disease affecting the brain and periphery.

 The classical (green arrows) and emerging (blue arrow) metabolic actions of GLP-1. Fig.1 The classical (green arrows) and emerging (blue arrow) metabolic actions of GLP-1. (Drucker, 2011)

GLP2R is expressed in the gut and closely related to the glucagon receptor and GLP1R. Glucagon-like peptide-2 (GLP2) is a 33-amino acid proglucagon-derived peptide produced by intestinal enteroendocrine cells. GLP2 stimulates intestinal growth and upregulates villus height in the small intestine, concomitant with increased crypt cell proliferation and decreased enterocyte apoptosis. Moreover, GLP2 prevents intestinal hypoplasia resulting from total parenteral nutrition.

Human Glucagon-like Peptide Receptor Members
GLP1R GLP2R

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Glucagon-Like Peptide Receptor Family

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Reference

  1. Drucker DJ, et al. (2011). Glucagon-like peptide-1 (GLP-1) receptor agonists, obesity, and psoriasis: diabetes meets dermatology. Diabetologia. 54(11): 2741-4.

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